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P Emery

Publications and source records attributed to P Emery.

At least 91 records · Page 5Linked to original sources
PubMed2003

Overexpression of transcripts containing LINE-1 in the synovia of patients with rheumatoid arthritis.

OBJECTIVE: To identify novel diagnostic markers by comparing gene expression in rheumatoid (RA) and reactive arthritis (ReA) synovium. METHODS: Synovial biopsy specimens were obtained by needle arthroscopy from the knees of 10 patients with either RA or ReA. RNA was isolated from the biopsy specimens and cDNA synthesised for analysis using a customised cDNA macroarray. Confirmatory analysis was performed using in situ hybridisation on a second set of synovial samples. RESULTS: Two unique transcripts (ReXS1 and fibronectin) were consistently more abundant in ReA and three homologous transcripts were more abundant in RA. The latter all mapped within long interspersed nucleotide elements (LINE-1), that form one of the families of repetitive sequences in the human genome. CONCLUSIONS: The abundance of transcripts containing LINE-1 in the RA synovium may be an epiphenomenon or may have pathogenic significance. Further work is required to determine the identity of the full length transcript(s) before its use as a diagnostic marker in RA can be assessed.

Adolescent↗
PubMed2002

Repeat-cycle study of high-dose intravenous 4162W94 anti-CD4 humanized monoclonal antibody in rheumatoid arthritis. A randomized placebo-controlled trial.

OBJECTIVE: Results of an earlier open-label pilot study showed that 4162W94 was a relatively non-depleting anti-CD4 monoclonal antibody that induced >80% down-modulation of CD4 molecules from the surface of T lymphocytes. This placebo-controlled repeat-cycle study was conducted in active rheumatoid arthritis (RA) patients to determine the duration of CD4 blockade required to achieve lasting clinical benefit. METHODS: Following DMARD washout, 48 patients (i.e. three cohorts of 16 patients) with ACR-defined RA were to be dosed with 1 (cohort 1), 2 (cohort 2) or 3 (cohort 3) cycles of 5x300 mg 4162W94 or placebo (12 and 4 patients per cohort respectively) at monthly intervals. There was at least 3 months of follow-up after dosing. Clinical outcome was assessed in evaluable patients (receiving at least 80% of each dose course) using ACR20 criteria (required on two consecutive visits). CD4 lymphocyte counts and adverse events were also monitored. RESULTS: Sixteen patients were dosed in each of the first two cohorts; however, the dose was reduced in cohort 3 after five patients had received up to two dose cycles due to accumulating evidence of a high frequency of skin rash. These patients were analysed according to the number of cycles received. A further eight patients received 5x100 mg for one to three cycles prior to stopping the study for administrative reasons. Four of 13 (P=0.119 vs placebo) and 7/13 (P=0.015 vs placebo) in cohorts 1 and 2 respectively achieved ACR20 response on at least two consecutive occasions. No patient receiving 5x100 mg/day or placebo achieved ACR20. Four patients were still responding at the end of the 3-month follow-up period. CD4 lymphocyte suppression (<0.2x10(9)/l on at least two successive occasions) occurred in 11/34 patients who received 4162W94 vs none on placebo. Rash occurred in 21/34 monoclonal antibody-treated patients, including one case of biopsy-confirmed cutaneous vasculitis and 1/11 placebo patients. CONCLUSION: 4162W94 demonstrated significant clinical efficacy in this study. However, because of unacceptable CD4 lymphopenia and rash, the original hypothesis that prolonged CD4 blockade would give lasting clinical benefit was not tested.

Adult↗
PubMed2002

Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide.

BACKGROUND: Effective treatment of active rheumatoid arthritis (RA) requires early diagnosis and early disease modifying antirheumatic drug (DMARD) treatment to have an impact on long term morbidity and mortality. Clinical criteria would facilitate early referral of the patient with suspected RA to a rheumatologist for definitive diagnosis and initiation of DMARD treatment at that point in the disease most likely to have an impact on the long term outcome. OBJECTIVE: To develop a referral recommendation that may serve as a clinical guide for primary care doctors, enabling them to identify patients with suspected RA during the early inflammatory stages. METHODS: Key points of the referral criteria were formed based on a thorough literature review targeting early RA, early arthritis clinics, DMARD treatment for early RA, prognostic factors of disease progression, early RA clinical trials, and quality of life. Evidence was graded using the methods defined by Shekelle et al. A draft version of the criterion was circulated among the authors for critical evaluation. A consensus integrated these comments. RESULTS: Clinical evidence strongly supports the observations that structural damage occurs early in active RA and that early DMARD treatment improves the long term outcome of the disease. The observations indicate that rapid referral to a rheumatologist is advised when RA is suspected. This may be supported by the presence of any of the following: >or=3 swollen joints, metatarsophalangeal/metacarpophalangeal involvement, and morning stiffness of >or=30 minutes. CONCLUSION: The proposed early referral recommendation is a viable tool for primary care doctors to identify potential patients with active RA early in the disease. Early referral to a rheumatologist for definitive diagnosis and early DMARD treatment should improve the long term outcome of RA.

Algorithms↗
PubMed2002

Which patients stop working because of rheumatoid arthritis? Results of five years' follow up in 732 patients from the Early RA Study (ERAS).

OBJECTIVES: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). SETTING: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. PATIENTS: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. METHODS: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. OUTCOME MEASURES: Changes in, and loss of paid work by five years' follow up. RESULTS: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. CONCLUSIONS: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.

Adult↗
PubMed2002

Histological assessment of the early enthesitis lesion in spondyloarthropathy.

OBJECTIVES: To describe the histological changes in acute enthesopathy in early spondyloarthropathies (SpA). METHODS: Clinically evident acute enthesopathy was confirmed by magnetic resonance imaging and ultrasonography in four cases of plantar fasciitis and one case of patellar tendon enthesitis. Ultrasound guided biopsy of insertional points was carried out with a Jamshedi needle. Control tissue was obtained from two subjects undergoing spinal grafting surgery. Standard histochemistry and immunohistochemistry analysis using the avidin-biotin immunoperoxidase complex method employing markers against CD3, CD8, CD34, and CD68 was used to determine cellular infiltrates at the insertion point. RESULTS: The enthesis architecture was abnormal in the SpA group, with increased vascularity and cellular infiltration compared with normal subjects. The predominant infiltrating cell at the enthesis fibrocartilage was the macrophage, but there was a paucity of lymphocytes at the insertion point. CONCLUSION: These preliminary findings have implications for a better understanding of the pathology in early SpA.

Adult↗
PubMed2002

Staging of patients with ankylosing spondylitis: a preliminary proposal.

Patients with ankylosing spondylitis (AS) are characterised by a wide range of clinical presentations, radiographic profiles, and outcomes, which are not well differentiated by current diagnostic and classification systems for the disorder. Inadequacies in these systems may limit clinicians' ability to manage their patients with AS appropriately and act as an obstacle to reasonable comparison of therapeutic trial results. A standardised staging system for AS is therefore proposed that would provide a more detailed categorisation of patients based on assessment of structural damage, peripheral joint and organ involvement, presence of concomitant diseases, and the severity and extent of disease activity and functional impairment. The proposed system needs to be evaluated closely and amended as needed to assure its usefulness in clinical and research settings.

Anti-Inflammatory Agents↗
PubMed2001

Prescribing in the UK.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Cyclooxygenase-2: a major therapeutic advance?

The introduction of the highly selective cyclooxygenase-2 (COX-2) inhibitors (Coxibs) has resulted in the greatest new drug use ever. The hypothesis on which these drugs were developed was that COX-2-specific inhibitors would retain the advantageous aspects but restrict the deleterious effects of conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Current practice and evidence suggests that bleeding from the gastrointestinal tract is reduced to the level of placebo and that dyspepsia persists, and in other areas (particularly renal side effects), COX-2-specific inhibitors still have classic NSAID problems.

Arthritis, Rheumatoid↗
PubMed2001

Predictors of outcome in patients with oligoarthritis: results of a protocol of intraarticular corticosteroids to all clinically active joints.

OBJECTIVE: To determine the outcome and the factors that predict the persistence of synovitis following intraarticular corticosteroid injections in patients with recent-onset oligoarthritis. METHODS: Fifty-one patients with < or =5 joints with synovitis (disease duration < or =12 months) were treated with intraarticular injections of methylprednisolone into all joints with clinical synovitis. Predictors of outcome were sought, with the primary end point a complete response (no synovitis on clinical examination) at 12 weeks. RESULTS: Patient's and physician's assessments of disease activity, the swollen joint count, and function (by Health Assessment Questionnaire) were all significantly improved at 12 weeks (P < 0.001). Twenty-nine patients (57%) were judged to have had a complete response at 2 weeks. The best predictor of response at 12 and 26 weeks was the presence or absence of synovitis at 2 weeks (P = 0.002 and P = 0.004, respectively). At 52 weeks of followup, nearly 50% of the patients still had evidence of synovitis. CONCLUSION: Intraarticular corticosteroids are an effective treatment for early oligoarthritis, but there is still a high level of long-term morbidity. Failure to respond by 2 weeks indicates a high likelihood of persistent disease, and this is relevant when producing management guidelines and selecting patients for studies focusing on early intervention.

Adult↗
PubMed2001

Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis.

OBJECTIVE: To examine matrix metalloproteinase 9 (MMP-9) in the synovial fluid (SF) and synovial membrane (SM) in relation to vascular endothelial cell (EC) apoptosis, vascular endothelial growth factor (VEGF), and SM vascular pattern. METHODS: Thirty-four patients underwent needle arthroscopy of the knee joint; 12 had early rheumatoid arthritis (RA), 12 had early psoriatic arthritis (PsA), and 10 had osteoarthritis (OA). The early RA and early PsA patients were matched for disease activity. SF levels of MMP-9 and VEGF were measured by an enzyme-linked immunosorbent assay, and EC apoptosis was measured by TUNEL assay. MMP-9 expression was examined in SM by immunohistochemistry. Synovial tissue explants were stimulated with VEGF, and MMP-9 levels were measured in the supernatants. The synovial vascular pattern was recorded. RESULTS: SF MMP-9 levels were significantly higher in early PsA patients than in early RA patients; OA patients had minimal levels. MMP-9 levels correlated with blood vessel morphology and SF VEGF levels. MMP-9 expression was greater in early PsA SM than in early RA SM, but the difference was not significant. In contrast however, EC apoptosis was greater in early RA SM than in early PsA SM. MMP-9 levels increased 2-fold and 9-fold, respectively, in SM explant culture supernatants on day 7 in response to stimulation with 25 ng/ml and 50 ng/ml of VEGF. CONCLUSION: SF MMP-9 levels correlate with the pattern of SM neovascularization and SF VEGF levels in early inflammatory arthritis, and VEGF increases MMP-9 production by SM. Endothelial cell apoptosis, however, appears to be more prevalent in early RA. This combination of factors may explain the pattern of differential angiogenesis in these arthritides.

Adult↗
PubMed2001

Efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthropathy: a clinical and magnetic resonance imaging study.

OBJECTIVE: To determine the effect of tumor necrosis factor alpha (TNFalpha) blockade with etanercept on the clinical manifestations of resistant spondylarthropathy (SpA) and on axial and peripheral entheseal lesions using magnetic resonance imaging (MRI). METHODS: We performed a descriptive longitudinal study of 10 SpA patients, all of whom had active inflammatory back pain and peripheral involvement. Patients were treated with 25 mg subcutaneous etanercept twice weekly for 6 months. Clinical assessments included entheseal count, visual analog scale (VAS) scores for spinal pain during the day and night, VAS scores for entheseal pain, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. MRI scans of sacroiliac (SI) joints, the lumbar spine, and affected peripheral joints were performed using a 1.5T scanner employing T1-weighted, T2-weighted fat-suppressed (FS), and T1-weighted FS postgadolinium sequences at baseline and at 6 months. Enthesitis and associated osteitis were scored semiquantitatively in pre- and posttreatment scans. RESULTS: There was a statistically significant improvement in all clinical and functional parameters (P = 0.008 for VAS spinal pain score during the day and for VAS spinal pain score during the night, P = 0.008 for the BASFI, and P = 0.005 for the BASDAI) as well as in quality of life (P = 0.005 for the ASQoL) at 6 months. Nine patients had a total of 44 MRI-detectable entheseal lesions. These were seen in the SI joints in 6 patients (n = 15 lesions), in the lumbar or cervical spine in 9 patients (n = 22 lesions), and in peripheral joints in 5 patients (n = 7 lesions). Overall, 86% of MRI-detected entheseal lesions either regressed completely or improved. No new lesions developed. CONCLUSION: These findings suggest that TNFalpha blockade with etanercept is markedly effective in controlling the clinical manifestations of SpA that is resistant to disease-modifying antirheumatic drugs. This is associated with marked improvement of enthesitis and associated osteitis pathology as determined by MRI.

Adult↗
PubMed2001

How do you diagnose rheumatoid arthritis early?

There are difficulties in making an accurate diagnosis of rheumatoid arthritis in its early stages, a principal problem being the fact that its most defining feature is chronicity, which, by definition, takes time to identify. There is substantial evidence that patients with rheumatoid arthritis should be treated early, and the majority are now commenced on therapy when first diagnosed. A logical implication of the early therapy approach is that treatment before rheumatoid arthritis is fully developed may have even greater benefits. This requires patients who are likely to have a persistent, more severe disease to be identified and treated effectively in the very earliest stages. This requires a system of the early specialist referral of suitable patients and the use of effective predictors of patient outcome. This text discusses the early arthritis clinic approach and the current evidence base available for use in constructing management guidelines for such patients.

Antirheumatic Agents↗